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Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber Composition.

Semenova, EA, Zempo, H, Miyamoto-Mikami, E, Kumagai, H, Larin, AK, Sultanov, RI, Babalyan, KA, Zhelankin, AV, Tobina, T, Shiose, K, Kakigi, R, Tsuzuki, T, Ichinoseki-Sekine, N, Kobayashi, H, Naito, H, Burniston, J, Generozov, EV, Fuku, N and Ahmetov, II (2022) Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber Composition. Cells, 11 (23). ISSN 2073-4409

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Open Access URL: https://doi.org/10.3390/cells11233910 (Published version)


Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10-5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10-15) and with greater appendicular lean mass (p = 1.2 × 10-5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.

Item Type: Article
Uncontrolled Keywords: DNA; GWAS; athletic performance; endurance; exercise; genetic markers; genotype; muscle fibers; sports; sprinters; talent identification; Humans; Genome-Wide Association Study; Muscle Fibers, Skeletal; Sports; Athletes; Muscle Fibers, Slow-Twitch; Cyclin-Dependent Kinase Inhibitor p21
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Divisions: Sport & Exercise Sciences
Publisher: MDPI AG
SWORD Depositor: A Symplectic
Date Deposited: 16 Dec 2022 10:09
Last Modified: 16 Dec 2022 10:15
DOI or ID number: 10.3390/cells11233910
URI: https://researchonline.ljmu.ac.uk/id/eprint/18416
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